Activation of transcription factor NF-kappa B in experimental glomerulonephritis in rats

Biochim Biophys Acta. 1996 Jun 7;1316(2):132-8. doi: 10.1016/0925-4439(96)00022-1.

Abstract

NF-kappa B plays a pivotal role in cells of the immune system as an inducible transcriptional activator. NF-kappa B regulates the transcription of many genes of pro-inflammatory cytokines and cell adhesion molecules, which could be involved in the pathogenesis of glomerulonephritis. Using a gel shift assay, we investigated NF-kappa B DNA-binding activity in glomeruli of WKY rats injected with nephrotoxic serum (NTS). Kinetic analysis indicated that the NF-kappa B DNA-binding activity in glomeruli, composed of p50 subunit determined by a supershift assay, increased on day 1 after NTS injection and the maximal activation was observed on day 3 to 5. NF-kappa B activation persisted at least until day 14. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappa B activation, inhibited the NTS-induced increase of glomerular NF-kappa B DNA-binding activity, followed by the inhibition of mRNA expression of IL-1 beta, MCP-1, ICAM-1 and iNOS, which are known to be regulated by NF-kappa B. PDTC also prevented urinary protein excretion which is a pathophysiological parameter for glomerulonephritis. These results suggest that NF-kappa B activation causes the induction of pro-inflammatory factors in nephritic glomeruli, which may play significant roles in the pathogenesis of glomerulonephritis.

MeSH terms

  • Animals
  • Base Sequence
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Glomerulonephritis / metabolism*
  • Male
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Oligonucleotides / chemistry
  • Proteinuria / chemically induced
  • Pyrrolidines / pharmacology
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred WKY
  • Reactive Oxygen Species / metabolism
  • Thiocarbamates / pharmacology

Substances

  • DNA-Binding Proteins
  • NF-kappa B
  • Oligonucleotides
  • Pyrrolidines
  • RNA, Messenger
  • Reactive Oxygen Species
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid
  • Nitric Oxide Synthase